In the two-part study, Joe Pagan, PhD, of Kentucky Equine Research in Versailles, Ky., also determined furosemide could enhance performance by reducing the rate of lactate buildup in the blood, an effect he attributes to the weight horses lose after receiving the diuretic. Pagan noted that this performance-enhancing effect had been revealed in previous studies.

He presented the findings this week at the Equine Science Society meeting, in Mescalero, N.M. Pagan said that because most previous studies have focused on furosemide's efficacy at preventing or reducing exercise-induced pulmonary hemorrhage, pulmonary physiologists typically have completed the work. Pagan wanted to assess how the drug affects horse nutritional balance.

In this study, researchers administered furosemide in the horses and then sent them through a controlled treadmill exercise test that started with a five-minute walk, then working at various speeds at two-minute intervals, and ended with four different gallop speeds at one-minute each.

Pagan and his team saw large sodium losses through urine 24 hours after administering furosemide then working the horses on the treadmill. They also noted similar losses of calcium. But two and three days later, the horses were able to move back into sodium balance by retaining more sodium rather than excreting it in their urine and manure. But the study horses did not retain more calcium to replenish their stores.

"With calcium, you don't see that bounce back like you did with sodium," Pagan said. "Calcium excretion remained high on the second and third days."

Pagan noted that horses in the study consumed calcium-rich feed, which prevented them from going into a negative calcium balance. He said the study indicates the animals would have faced a negative balance if given only the daily recommended amounts of calcium or less.

"That sort of threw up the red flag because calcium is what the body uses to build bone strength," Pagan said. "The important thing is that they showed deficits for more than 24 hours. You'd expect them to show deficits for 24 hours, but the lingering deficit is something we have to address."

Pagan cautioned that the study does not make any correlation between calcium loss and breakdowns.

"The reality is we have no idea," Pagan said. "To do that study would be a very big, very expensive study."

Still, Pagan believes his study indicates calcium loss is a topic worthy of more investigation. He said that because calcium levels must be maintained in the blood, a horse with negative calcium balance could draw on calcium from his bones to maintain those levels.

Pagan also evaluated lactic acid buildup in six horses with an average age of 7, each of which participated in all three study groups: horses not receiving furosemide (untreated controls), and horses getting furosemide under two different nutritional intake categories.

In working the furosemide-treated horses on the treadmill, the researchers noted that the drug enhanced performance by reducing the buildup of lactic acid, which is associated with fatigue, in the blood. Pagan attributes this improved performance to the horses' weight loss. Horses given furosemide and then exercised on the treadmill lost an average of 40 pounds.

Also, lactic acid took longer to build up in the blood in horses on furosemide as opposed to those not receiving the diuretic. Pagan believes this was caused by the weight loss; an alkalizing effect, as "milkshaking" a horse, for instance, promotes, the opposite effect, moving lactic acid from muscles to the blood.

"This is a body weight phenomenon," Pagan said of the performance spike indicated in horses who had received furosemide. "When horses were given Lasix, they produced less lactic acid and relied less on anaerobic pathways than aerobic. They used less oxygen. So their total efficiency was better all the way through."

Knowing that, Pagan said perhaps a formula for adding weight to horses on furosemide could balance out the performance-enhancing aspects of the diuretic when they race against horses not on furosemide. He is considering a follow-up study in which he adds weight to horses on Salix to see if that cancels out the delayed fatigue.

Pagan said some experts have tied increased lactic acid levels in blood, and the resulting fatigue, to breakdowns. He said one could argue the lower levels of lactic acid in the blood for horses treated with furosemide could help reduce the rate of breakdowns, but he added that more study would be needed with horses in race conditions.

"A pro-Lasix person could argue that if Lasix reduces lactic acid, and lactic acid contributes to breakdowns; then giving Lasix is protective," Pagan said. "The problem with that argument, though, is it assumes the horse is running at the same speed. In the real world, the horse would run faster until it got the same amount of lactate."

In looking at the weight loss associated with furosemide, horses in the study were able to rebound quickly, typically regaining the weight within eight hours through increased water intake. Again, Pagan noted that a study in race conditions could be more indicative.

"This study did not support the idea that Lasix knocks them for a loop and it takes them weeks and weeks to recover that body weight," Pagan said. "It wasn't a Thoroughbred race though. It was a lot longer (run) than a Thoroughbred race but we controlled the speed. So it's not apples to apples."

As for the calcium loss, Pagan noted that supplementing calcium for the horses may not be enough to address the problem. "You've got to send signals to both the kidney and the intestine that you've got to retain this calcium,” he said, explaining that he and colleagues are working to find solutions for this, getting calcium to “act like sodium,” whereby horses lose some of it in their urine but can recoup it more quickly.

About the Author

Frank Angst is a staff writer for The Blood-Horse magazine. An American Horse Publications three-time winner in best news story category, Angst has covered horse racing for more than a decade. Angst spent ten years at Thoroughbred Times, where he earned awards as that magazine’s senior writer and helped launch Thoroughbred Times TODAY. Besides covering horse racing, Angst enjoys handicapping. Angst has written about sports for more than 20 years, including several seasons covering a nationally ranked Marshall Thundering Herd football team.

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